Re: [gmx-users] enegry minimisation
- Original Message - From: sonali dhindwal sonali11dhind...@yahoo.co.in Date: Friday, May 21, 2010 15:38 Subject: Re: [gmx-users] enegry minimisation To: jalem...@vt.edu, Discussion list for GROMACS users gmx-users@gromacs.org --- | hello Jusitn, Thanks for your reply,, I am sending you the link, so that you can see the changes in the protein, I have specifically shown that part of the protein, where I am seeing changes, http://picasaweb.google.co.in/sonali11dhindwal/Protein?feat=directlink Yello beeta sheets are of the protein after EM, and magenta are that of the refrence structure, you can see how this time,I am surprised myself that sheets have become longer than the refrence structure. I have corrected that define = -DPOSRES also. and have taken that posres file generated by pdb2gmx.is this the problem of the visualiser I m using, I am using pymol for it I wouldn't describe what I can see there as significant change. The criterion any visualization program uses for assigning beta-strand vs not-strand is a reasonably arbitrary choice, and might differ between programs. It's quite plausible that EM could see a residue here and there cross a boundary if they were originally close. Looking at all-atom or heavy-atom RMSD before and after EM (and maybe RMSD also over the subset of atoms of direct interest) is a much more reliable indicator that nothing has gone wrong. Off the top of my head, for a protein with no disordered regions, I'd expect EM on an experimental structure and normal force field to move about or less than 0.02nm on heavy-atom RMSD. All the EM is really expected to do is (e.g.) make sensible the hydrogen atoms whose positions were inferred or generated. Mark -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php
Re: [gmx-users] enegry minimisation
Hello Gaurav, Thanks for your reply, I did position restrained enegry minimisation, and used following .mdp file for the same title = protein cpp = /usr/bin/cpp ; the c pre-processor define = -DPOSRE constraints = none integrator = steep dt = 0.002 ; ps ! nsteps = 1000 nstlist = 10 ns_type = grid rlist = 0.9 coulombtype = PME rcoulomb = 0.9 rvdw = 0.9 fourierspacing = 0.12 fourier_nx = 0 fourier_ny = 0 fourier_nz = 0 pme_order = 4 ewald_rtol = 1e-5 optimize_fft = yes ; ; Energy minimizing stuff ; emtol = 1000.0 emstep = 0.01 pbc = xyz I included define = -DPOSRE, for restraining the atom postion, I used posre.itp which was genertaed by pdb2gmx. Have I done it correctly, because after this also many of the beeta sheets have become short, forming loops. I also want to ask what is the meaning of fx fy and fz : ; atom type fx fy fz 1 1 1000 1000 1000 5 1 1000 1000 1000 6 1 1000 1000 1000 7 1 1000 1000 1000 8 1 1000 1000 1000 9 1 1000 1000 1000 11 1 1000 1000 1000 12 1 1000 1000 1000 15 1 1000 1000 1000 18 1 1000 1000 1000 19 1 1000 1000 1000 20 1 1000 1000 1000 21 1 1000 1000 1000 22 1 1000 1000 1000 23 1 1000 1000 1000 which is there in posre.itp file, and if these should have value of 1000 1000 1000 each ? Thanks in advance. -- Sonali Dhindwal --- On Wed, 19/5/10, Gaurav Goel gauravgoel...@gmail.com wrote: From: Gaurav Goel gauravgoel...@gmail.com Subject: Re: [gmx-users] enegry minimisation To: sonali dhindwal sonali11dhind...@yahoo.co.in Date: Wednesday, 19 May, 2010, 8:39 PM For position restraints you need to do the following: 1. define a name.itp file which looks like: ; In this topology include file, you will find position restraint ; entries for all the heavy atoms in your original pdb file. ; This means that all the protons which were added by pdb2gmx are ; not restrained. [ position_restraints ] ; atom type fx fy fz 1 1 1000 1000 1000 5 1 1000 1000 1000 6 1 1000 1000 1000 ... ... _ 1,5,6 etc. are the atom indices you want to restrain. section 4.3.1 in manual. 2. Add define = -Dname to your mdp file 3. Add following lines to your topology file ; Include Position restraint file #ifdef name #include name.itp #endif 4. compile and run. I'm sure you will find mroe information on position-restrain simulation on gmx-users archive. -Gaurav On Wed, May 19, 2010 at 10:26 AM, sonali dhindwal sonali11dhind...@yahoo.co.in wrote: Hello Gaurav, Can you please help me in suggesting where should I look for providing parameters to constrain the protein backbone and then do EM and then how to run a short MD simulation by constraining the protein backbone. Sorry to bother you, but as I am new to Gromacs, your help will be highly appreciable. Thanks in advance -- Sonali Dhindwal --- On Wed, 19/5/10, Gaurav Goel gauravgoel...@gmail.com wrote: From: Gaurav Goel gauravgoel...@gmail.com Subject: Re: [gmx-users] enegry minimisation To: Discussion list for GROMACS users gmx-users@gromacs.org Date: Wednesday, 19 May, 2010, 6:44 PM After adding water you can do energy minimization (EM) in two steps: 1. Constrain the protein backbone and do EM. 2. Now do EM on the full system. 3. Run a short MD simulation by constraining the protein backbone. The above three steps will help hydrate the protein molecule with minimal distortion of protein structure. 4. Now run a MD on full system. for details looks here: http://www.google.com/url?sa=tsource=webct=rescd=2ved=0CBcQFjABurl=http%3A%2F%2Feugen.leitl.org%2Fchem%2Fkerrigje%2Fpdf_files%2Ffwspidr_tutor.pdfei=jOPzS8a3Lab2MdX1_aAOusg=AFQjCNGB_3mXSQRHuqehBSHXsRyXP1Gymgsig2=bY3NqXHmruR7eSLVyAuCHQ -Gaurav On Wed, May 19, 2010 at 8:18 AM, sonali dhindwal sonali11dhind...@yahoo.co.in wrote: Sorry, but I couldnt get your question, I have used this .mdp file for energy minimisation after addition of water and using GROMOS96 43a1 force field : title= drg_trp cpp = /lib/cpp ; location of cpp on SGI define = -DFLEX_SPC ; Use Ferguson’s Flexible water model [4] constraints = none integrator = steep dt = 0.002; ps ! nsteps = 2000 nstlist = 10 ns_type = grid rlist= 0.9 coulombtype = PME ; Use particle-mesh ewald rcoulomb = 0.9 rvdw = 1.0 fourierspacing = 0.12 fourier_nx = 0 fourier_ny = 0 fourier_nz = 0 pme_order = 4 ewald_rtol = 1e-5 optimize_fft = yes ; ; Energy minimizing stuff ; emtol
Re: [gmx-users] enegry minimisation
sonali dhindwal wrote: Hello Gaurav, Thanks for your reply, I did position restrained enegry minimisation, and used following .mdp file for the same title= protein cpp = /usr/bin/cpp ; the c pre-processor define = -DPOSRE constraints = none integrator = steep dt = 0.002; ps ! nsteps = 1000 nstlist = 10 ns_type = grid rlist= 0.9 coulombtype = PME rcoulomb = 0.9 rvdw = 0.9 fourierspacing = 0.12 fourier_nx = 0 fourier_ny = 0 fourier_nz = 0 pme_order= 4 ewald_rtol = 1e-5 optimize_fft = yes ; ; Energy minimizing stuff ; emtol= 1000.0 emstep = 0.01 pbc= xyz I included define = -DPOSRE, for restraining the atom postion, I used posre.itp which was genertaed by pdb2gmx. Have I done it correctly, because after this also many of the beeta sheets have become short, forming loops. Well, you haven't properly defined position restraints. The default (produced by pdb2gmx) requires define = -DPOSRES not -DPOSRE. If you have for some reason modified the topology, then maybe your approach is correct, but otherwise your position restraints are not being applied. I also find it very curious that such substantial changes are taking place during a simple energy minimization. Are you sure the effects you are seeing are not simply due to the visualization software you are using guessing the incorrect secondary structure type? I have had that experience numerous times, especially in the case of beta-strands. DSSP tells me that, geometrically, I have beta-strands, but the visualization software renders coil structures. In any case, large structural deviations during EM suggest something fundamentally wrong with the model. Usually the changes in EM are small, since it is performed at 0 K. Only huge forces would cause any sort of structural change. I also want to ask what is the meaning of fx fy and fz : Force constants (kJ mol^-1 nm^-2) in the x, y, and z directions. ; atom type fx fy fz 1 1 1000 1000 1000 5 1 1000 1000 1000 6 1 1000 1000 1000 7 1 1000 1000 1000 8 1 1000 1000 1000 9 1 1000 1000 1000 11 1 1000 1000 1000 12 1 1000 1000 1000 15 1 1000 1000 1000 18 1 1000 1000 1000 19 1 1000 1000 1000 20 1 1000 1000 1000 21 1 1000 1000 1000 22 1 1000 1000 1000 23 1 1000 1000 1000 which is there in posre.itp file, and if these should have value of 1000 1000 1000 each ? These default values are typically quite sufficient to restrain the structure. -Justin Thanks in advance. -- Sonali Dhindwal --- On *Wed, 19/5/10, Gaurav Goel /gauravgoel...@gmail.com/* wrote: From: Gaurav Goel gauravgoel...@gmail.com Subject: Re: [gmx-users] enegry minimisation To: sonali dhindwal sonali11dhind...@yahoo.co.in Date: Wednesday, 19 May, 2010, 8:39 PM For position restraints you need to do the following: 1. define a name.itp file which looks like: ; In this topology include file, you will find position restraint ; entries for all the heavy atoms in your original pdb file. ; This means that all the protons which were added by pdb2gmx are ; not restrained. [ position_restraints ] ; atom type fx fy fz 1 1 1000 1000 1000 5 1 1000 1000 1000 6 1 1000 1000 1000 ... ... _ 1,5,6 etc. are the atom indices you want to restrain. section 4.3.1 in manual. 2. Add define = -Dname to your mdp file 3. Add following lines to your topology file ; Include Position restraint file #ifdef name #include name.itp #endif 4. compile and run. I'm sure you will find mroe information on position-restrain simulation on gmx-users archive. -Gaurav On Wed, May 19, 2010 at 10:26 AM, sonali dhindwal sonali11dhind...@yahoo.co.in /mc/compose?to=sonali11dhind...@yahoo.co.in wrote: Hello Gaurav, Can you please help me in suggesting where should I look for providing parameters to constrain the protein backbone and then do EM and then how to run a short MD simulation by constraining the protein backbone. Sorry to bother you, but as I am new to Gromacs, your help will be highly appreciable. Thanks in advance -- Sonali Dhindwal --- On *Wed, 19/5/10, Gaurav Goel /gauravgoel...@gmail.com /mc/compose?to=gauravgoel...@gmail.com/* wrote: From: Gaurav Goel gauravgoel...@gmail.com /mc/compose?to=gauravgoel...@gmail.com Subject: Re: [gmx-users] enegry minimisation To: Discussion list for GROMACS users gmx-users@gromacs.org /mc/compose
Re: [gmx-users] enegry minimisation
Can you try using g_rms to compare the difference between the structures before and after EM. -Gaurav On Thu, May 20, 2010 at 7:53 AM, Justin A. Lemkul jalem...@vt.edu wrote: sonali dhindwal wrote: Hello Gaurav, Thanks for your reply, I did position restrained enegry minimisation, and used following .mdp file for the same title = protein cpp = /usr/bin/cpp ; the c pre-processor define = -DPOSRE constraints = none integrator = steep dt = 0.002 ; ps ! nsteps = 1000 nstlist = 10 ns_type = grid rlist = 0.9 coulombtype = PME rcoulomb = 0.9 rvdw = 0.9 fourierspacing = 0.12 fourier_nx = 0 fourier_ny = 0 fourier_nz = 0 pme_order = 4 ewald_rtol = 1e-5 optimize_fft = yes ; ; Energy minimizing stuff ; emtol = 1000.0 emstep = 0.01 pbc = xyz I included define = -DPOSRE, for restraining the atom postion, I used posre.itp which was genertaed by pdb2gmx. Have I done it correctly, because after this also many of the beeta sheets have become short, forming loops. Well, you haven't properly defined position restraints. The default (produced by pdb2gmx) requires define = -DPOSRES not -DPOSRE. If you have for some reason modified the topology, then maybe your approach is correct, but otherwise your position restraints are not being applied. I also find it very curious that such substantial changes are taking place during a simple energy minimization. Are you sure the effects you are seeing are not simply due to the visualization software you are using guessing the incorrect secondary structure type? I have had that experience numerous times, especially in the case of beta-strands. DSSP tells me that, geometrically, I have beta-strands, but the visualization software renders coil structures. In any case, large structural deviations during EM suggest something fundamentally wrong with the model. Usually the changes in EM are small, since it is performed at 0 K. Only huge forces would cause any sort of structural change. I also want to ask what is the meaning of fx fy and fz : Force constants (kJ mol^-1 nm^-2) in the x, y, and z directions. ; atom type fx fy fz 1 1 1000 1000 1000 5 1 1000 1000 1000 6 1 1000 1000 1000 7 1 1000 1000 1000 8 1 1000 1000 1000 9 1 1000 1000 1000 11 1 1000 1000 1000 12 1 1000 1000 1000 15 1 1000 1000 1000 18 1 1000 1000 1000 19 1 1000 1000 1000 20 1 1000 1000 1000 21 1 1000 1000 1000 22 1 1000 1000 1000 23 1 1000 1000 1000 which is there in posre.itp file, and if these should have value of 1000 1000 1000 each ? These default values are typically quite sufficient to restrain the structure. -Justin Thanks in advance. -- Sonali Dhindwal --- On *Wed, 19/5/10, Gaurav Goel /gauravgoel...@gmail.com/* wrote: From: Gaurav Goel gauravgoel...@gmail.com Subject: Re: [gmx-users] enegry minimisation To: sonali dhindwal sonali11dhind...@yahoo.co.in Date: Wednesday, 19 May, 2010, 8:39 PM For position restraints you need to do the following: 1. define a name.itp file which looks like: ; In this topology include file, you will find position restraint ; entries for all the heavy atoms in your original pdb file. ; This means that all the protons which were added by pdb2gmx are ; not restrained. [ position_restraints ] ; atom type fx fy fz 1 1 1000 1000 1000 5 1 1000 1000 1000 6 1 1000 1000 1000 ... ... _ 1,5,6 etc. are the atom indices you want to restrain. section 4.3.1 in manual. 2. Add define = -Dname to your mdp file 3. Add following lines to your topology file ; Include Position restraint file #ifdef name #include name.itp #endif 4. compile and run. I'm sure you will find mroe information on position-restrain simulation on gmx-users archive. -Gaurav On Wed, May 19, 2010 at 10:26 AM, sonali dhindwal sonali11dhind...@yahoo.co.in /mc/compose?to=sonali11dhind...@yahoo.co.in wrote: Hello Gaurav, Can you please help me in suggesting where should I look for providing parameters to constrain the protein backbone and then do EM and then how to run a short MD simulation by constraining the protein backbone. Sorry to bother you, but as I am new to Gromacs, your help will be highly appreciable. Thanks in advance -- Sonali Dhindwal --- On *Wed, 19/5/10, Gaurav Goel /gauravgoel...@gmail.com /mc/compose?to=gauravgoel...@gmail.com/* wrote: From: Gaurav Goel gauravgoel
Re: [gmx-users] enegry minimisation
Hello Gaurav, when i did g_rms with structre before energy minimisation as refrence and strucutre after energy minimisation, it came to be around 0.02. -- Sonali Dhindwal --- On Thu, 20/5/10, Gaurav Goel gauravgoel...@gmail.com wrote: From: Gaurav Goel gauravgoel...@gmail.com Subject: Re: [gmx-users] enegry minimisation To: jalem...@vt.edu, Discussion list for GROMACS users gmx-users@gromacs.org Date: Thursday, 20 May, 2010, 5:36 PM Can you try using g_rms to compare the difference between the structures before and after EM. -Gaurav On Thu, May 20, 2010 at 7:53 AM, Justin A. Lemkul jalem...@vt.edu wrote: sonali dhindwal wrote: Hello Gaurav, Thanks for your reply, I did position restrained enegry minimisation, and used following .mdp file for the same title= protein cpp = /usr/bin/cpp ; the c pre-processor define = -DPOSRE constraints = none integrator = steep dt = 0.002; ps ! nsteps = 1000 nstlist = 10 ns_type = grid rlist= 0.9 coulombtype = PME rcoulomb = 0.9 rvdw = 0.9 fourierspacing = 0.12 fourier_nx = 0 fourier_ny = 0 fourier_nz = 0 pme_order= 4 ewald_rtol = 1e-5 optimize_fft = yes ; ; Energy minimizing stuff ; emtol= 1000.0 emstep = 0.01 pbc= xyz I included define = -DPOSRE, for restraining the atom postion, I used posre.itp which was genertaed by pdb2gmx. Have I done it correctly, because after this also many of the beeta sheets have become short, forming loops. Well, you haven't properly defined position restraints. The default (produced by pdb2gmx) requires define = -DPOSRES not -DPOSRE. If you have for some reason modified the topology, then maybe your approach is correct, but otherwise your position restraints are not being applied. I also find it very curious that such substantial changes are taking place during a simple energy minimization. Are you sure the effects you are seeing are not simply due to the visualization software you are using guessing the incorrect secondary structure type? I have had that experience numerous times, especially in the case of beta-strands. DSSP tells me that, geometrically, I have beta-strands, but the visualization software renders coil structures. In any case, large structural deviations during EM suggest something fundamentally wrong with the model. Usually the changes in EM are small, since it is performed at 0 K. Only huge forces would cause any sort of structural change. I also want to ask what is the meaning of fx fy and fz : Force constants (kJ mol^-1 nm^-2) in the x, y, and z directions. ; atom type fx fy fz 1 1 1000 1000 1000 5 1 1000 1000 1000 6 1 1000 1000 1000 7 1 1000 1000 1000 8 1 1000 1000 1000 9 1 1000 1000 1000 11 1 1000 1000 1000 12 1 1000 1000 1000 15 1 1000 1000 1000 18 1 1000 1000 1000 19 1 1000 1000 1000 20 1 1000 1000 1000 21 1 1000 1000 1000 22 1 1000 1000 1000 23 1 1000 1000 1000 which is there in posre.itp file, and if these should have value of 1000 1000 1000 each ? These default values are typically quite sufficient to restrain the structure. -Justin Thanks in advance. -- Sonali Dhindwal --- On *Wed, 19/5/10, Gaurav Goel /gauravgoel...@gmail.com/* wrote: From: Gaurav Goel gauravgoel...@gmail.com Subject: Re: [gmx-users] enegry minimisation To: sonali dhindwal sonali11dhind...@yahoo.co.in Date: Wednesday, 19 May, 2010, 8:39 PM For position restraints you need to do the following: 1. define a name.itp file which looks like: ; In this topology include file, you will find position restraint ; entries for all the heavy atoms in your original pdb file. ; This means that all the protons which were added by pdb2gmx are ; not restrained. [ position_restraints ] ; atom type fx fy fz 1 1 1000 1000 1000 5 1 1000 1000 1000 6 1 1000 1000 1000 ... ... _ 1,5,6 etc. are the atom indices you want to restrain. section 4.3.1 in manual. 2. Add define = -Dname to your mdp file 3. Add following lines to your topology file ; Include Position restraint file #ifdef name #include name.itp #endif 4. compile and run. I'm sure you will find mroe information on position-restrain simulation on gmx-users archive. -Gaurav On Wed, May 19, 2010 at 10:26 AM, sonali dhindwal sonali11dhind...@yahoo.co.in /mc/compose?to=sonali11dhind...@yahoo.co.in wrote: Hello Gaurav, Can you please help me in suggesting where should I look for providing parameters to constrain the protein backbone
Re: [gmx-users] enegry minimisation
sonali dhindwal wrote: Hello Gaurav, when i did g_rms with structre before energy minimisation as refrence and strucutre after energy minimisation, it came to be around 0.02. Is that backbone RMSD or does it consider all protein atoms? In either case, a value of 0.02 indicates a very small amount of change in the protein structure, which makes it very hard to believe that any large-scale alteration of the secondary structure is happening. -Justin -- Sonali Dhindwal --- On *Thu, 20/5/10, Gaurav Goel /gauravgoel...@gmail.com/* wrote: From: Gaurav Goel gauravgoel...@gmail.com Subject: Re: [gmx-users] enegry minimisation To: jalem...@vt.edu, Discussion list for GROMACS users gmx-users@gromacs.org Date: Thursday, 20 May, 2010, 5:36 PM Can you try using g_rms to compare the difference between the structures before and after EM. -Gaurav On Thu, May 20, 2010 at 7:53 AM, Justin A. Lemkul jalem...@vt.edu /mc/compose?to=jalem...@vt.edu wrote: sonali dhindwal wrote: Hello Gaurav, Thanks for your reply, I did position restrained enegry minimisation, and used following .mdp file for the same title = protein cpp = /usr/bin/cpp ; the c pre-processor define = -DPOSRE constraints = none integrator = steep dt = 0.002 ; ps ! nsteps = 1000 nstlist = 10 ns_type = grid rlist = 0.9 coulombtype = PME rcoulomb = 0.9 rvdw = 0.9 fourierspacing = 0.12 fourier_nx = 0 fourier_ny = 0 fourier_nz = 0 pme_order = 4 ewald_rtol = 1e-5 optimize_fft = yes ; ; Energy minimizing stuff ; emtol = 1000.0 emstep = 0.01 pbc = xyz I included define = -DPOSRE, for restraining the atom postion, I used posre.itp which was genertaed by pdb2gmx. Have I done it correctly, because after this also many of the beeta sheets have become short, forming loops. Well, you haven't properly defined position restraints. The default (produced by pdb2gmx) requires define = -DPOSRES not -DPOSRE. If you have for some reason modified the topology, then maybe your approach is correct, but otherwise your position restraints are not being applied. I also find it very curious that such substantial changes are taking place during a simple energy minimization. Are you sure the effects you are seeing are not simply due to the visualization software you are using guessing the incorrect secondary structure type? I have had that experience numerous times, especially in the case of beta-strands. DSSP tells me that, geometrically, I have beta-strands, but the visualization software renders coil structures. In any case, large structural deviations during EM suggest something fundamentally wrong with the model. Usually the changes in EM are small, since it is performed at 0 K. Only huge forces would cause any sort of structural change. I also want to ask what is the meaning of fx fy and fz : Force constants (kJ mol^-1 nm^-2) in the x, y, and z directions. ; atom type fx fy fz 1 1 1000 1000 1000 5 1 1000 1000 1000 6 1 1000 1000 1000 7 1 1000 1000 1000 8 1 1000 1000 1000 9 1 1000 1000 1000 11 1 1000 1000 1000 12 1 1000 1000 1000 15 1 1000 1000 1000 18 1 1000 1000 1000 19 1 1000 1000 1000 20 1 1000 1000 1000 21 1 1000 1000 1000 22 1 1000 1000 1000 23 1 1000 1000 1000 which is there in posre.itp file, and if these should have value of 1000 1000 1000 each ? These default values are typically quite sufficient to restrain the structure. -Justin Thanks in advance. -- Sonali Dhindwal --- On *Wed, 19/5/10, Gaurav Goel /gauravgoel...@gmail.com /mc/compose?to=gauravgoel...@gmail.com/* wrote: From: Gaurav Goel gauravgoel...@gmail.com /mc/compose?to=gauravgoel...@gmail.com Subject: Re: [gmx-users] enegry minimisation To: sonali dhindwal sonali11dhind...@yahoo.co.in /mc/compose?to=sonali11dhind...@yahoo.co.in Date: Wednesday, 19 May, 2010, 8:39 PM For position restraints you need to do the following: 1. define a name.itp file which looks like: ; In this topology include file, you will find position restraint ; entries for all the heavy atoms in your original pdb file. ; This means that all the protons which were added by pdb2gmx are ; not restrained. [ position_restraints ] ; atom type fx fy fz 1 1 1000 1000 1000 5 1 1000 1000 1000 6 1 1000 1000 1000
Re: [gmx-users] enegry minimisation
sonali dhindwal wrote: Thanks for your reply Justin, this is rms for protein backbone, it is showing as 0.02 but when i check it in pymol by aligning two molecules rms is 0.256, and there is change in the structre of the protein. Sounds like that's the same result (potentially). Gromacs uses nm for RMSD, maybe PyMOL uses Angstrom? Can you render an image and post it? I can't really grasp what's happening without seeing it. EM should not be making large changes to your structure, and a backbone RMSD of 0.02 nm does not sound like enough to cause serious distortion. Instructions for sharing the image (should you choose to provide it) can be found here (bullet point #4): http://www.gromacs.org/Support/Mailing_Lists#Mailing_List_Etiquette -Justin Regards -- Sonali Dhindwal --- On *Thu, 20/5/10, Justin A. Lemkul /jalem...@vt.edu/* wrote: From: Justin A. Lemkul jalem...@vt.edu Subject: Re: [gmx-users] enegry minimisation To: Discussion list for GROMACS users gmx-users@gromacs.org Date: Thursday, 20 May, 2010, 6:46 PM sonali dhindwal wrote: Hello Gaurav, when i did g_rms with structre before energy minimisation as refrence and strucutre after energy minimisation, it came to be around 0.02. Is that backbone RMSD or does it consider all protein atoms? In either case, a value of 0.02 indicates a very small amount of change in the protein structure, which makes it very hard to believe that any large-scale alteration of the secondary structure is happening. -Justin -- Sonali Dhindwal --- On *Thu, 20/5/10, Gaurav Goel /gauravgoel...@gmail.com /mc/compose?to=gauravgoel...@gmail.com/* wrote: From: Gaurav Goel gauravgoel...@gmail.com /mc/compose?to=gauravgoel...@gmail.com Subject: Re: [gmx-users] enegry minimisation To: jalem...@vt.edu /mc/compose?to=jalem...@vt.edu, Discussion list for GROMACS users gmx-users@gromacs.org /mc/compose?to=gmx-us...@gromacs.org Date: Thursday, 20 May, 2010, 5:36 PM Can you try using g_rms to compare the difference between the structures before and after EM. -Gaurav On Thu, May 20, 2010 at 7:53 AM, Justin A. Lemkul jalem...@vt.edu /mc/compose?to=jalem...@vt.edu /mc/compose?to=jalem...@vt.edu /mc/compose?to=jalem...@vt.edu wrote: sonali dhindwal wrote: Hello Gaurav, Thanks for your reply, I did position restrained enegry minimisation, and used following .mdp file for the same title = protein cpp = /usr/bin/cpp ; the c pre-processor define = -DPOSRE constraints = none integrator = steep dt = 0.002 ; ps ! nsteps = 1000 nstlist = 10 ns_type = grid rlist = 0.9 coulombtype = PME rcoulomb = 0.9 rvdw = 0.9 fourierspacing = 0.12 fourier_nx = 0 fourier_ny = 0 fourier_nz = 0 pme_order = 4 ewald_rtol = 1e-5 optimize_fft = yes ; ; Energy minimizing stuff ; emtol = 1000.0 emstep = 0.01 pbc = xyz I included define = -DPOSRE, for restraining the atom postion, I used posre.itp which was genertaed by pdb2gmx. Have I done it correctly, because after this also many of the beeta sheets have become short, forming loops. Well, you haven't properly defined position restraints. The default (produced by pdb2gmx) requires define = -DPOSRES not -DPOSRE. If you have for some reason modified the topology, then maybe your approach is correct, but otherwise your position restraints are not being applied. I also find it very curious that such substantial changes are taking place during a simple energy minimization. Are you sure the effects you are seeing are not simply due to the visualization software you are using guessing the incorrect secondary structure type? I have had that experience numerous times, especially in the case of beta-strands. DSSP tells me that, geometrically, I have beta-strands, but the visualization software renders coil structures. In any case, large structural deviations during EM suggest something fundamentally wrong with the model. Usually the changes in EM are small, since it is performed at 0 K. Only huge
Re: [gmx-users] enegry minimisation
hello Jusitn, Thanks for your reply,, I am sending you the link, so that you can see the changes in the protein, I have specifically shown that part of the protein, where I am seeing changes, http://picasaweb.google.co.in/sonali11dhindwal/Protein?feat=directlink Yello beeta sheets are of the protein after EM, and magenta are that of the refrence structure, you can see how this time,I am surprised myself that sheets have become longer than the refrence structure. I have corrected that define = -DPOSRES also. and have taken that posres file generated by pdb2gmx.is this the problem of the visualiser I m using, I am using pymol for it Thanks -- Sonali Dhindwal -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php
Re: [gmx-users] enegry minimisation
sonali dhindwal wrote: Hello All This question may sound trivial to many, but as i am new to this field, please help. I want to ask a question regarding my previous query of distortion of protein strucutre after molecular dynamcs simulation. Can you provide a link to your previous post, for reference? I have noticed that after enegry minimisation using steepest decent algorithm, using emtol of 1000 kJ mol^-1 nm^-1 . So is it necessary to do enegry minimisation step before MD, because this is my modeled protein, and i have already done energy minimisation using different program and after that I have done refinement also. Have you added solvent or anything else to the protein model? If so, then the answer is yes. Solvation with a regularly-ordered lattice of solvent molecules can (and often does) lead to bad clashes with your protein structure, thus necessitating further minimization. There are plenty of reasons why a protein structure might be unstable, most of them related to .mdp file settings, but you haven't posted those so there's no way to know if you're doing things correctly. -Justin Thanks and regards ^ -- Sonali Dhindwal -- Justin A. Lemkul Ph.D. Candidate ICTAS Doctoral Scholar MILES-IGERT Trainee Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu | (540) 231-9080 http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php
Re: [gmx-users] enegry minimisation
sonali dhindwal skrev: Hello All This question may sound trivial to many, but as i am new to this field, please help. I want to ask a question regarding my previous query of distortion of protein strucutre after molecular dynamcs simulation. I have noticed that after enegry minimisation using steepest decent algorithm, using emtol of 1000 kJ mol^-1 nm^-1 . So is it necessary to do enegry minimisation step before MD, because this is my modeled protein, and i have already done energy minimisation using different program and after that I have done refinement also. Thanks and regards ^ -- Sonali Dhindwal That depends how that minimization was carried out. Did it use the same forcefield parameters and the same boxsize etc., then in principle no. If not, then I strongly suggest doing EM before MD to prevent problems later on. I don't understand what it is that you noticed after energy minimization. Cheers, -- --- Erik Marklund, PhD student Dept. of Cell and Molecular Biology, Uppsala University. Husargatan 3, Box 596,75124 Uppsala, Sweden phone:+46 18 471 4537fax: +46 18 511 755 er...@xray.bmc.uu.sehttp://folding.bmc.uu.se/ -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php
Re: [gmx-users] enegry minimisation
sonali dhindwal skrev: Hello All This question may sound trivial to many, but as i am new to this field, please help. I want to ask a question regarding my previous query of distortion of protein strucutre after molecular dynamcs simulation. I have noticed that after enegry minimisation using steepest decent algorithm, using emtol of 1000 kJ mol^-1 nm^-1 , large amount of distortion occurs. So is it necessary to do enegry minimisation step before MD, because this is my modeled protein, and i have already done energy minimisation using different program and after that I have done refinement also. Thanks and regards ^ -- Sonali Dhindwal So how has your system setup changed since your previous EM? Addition of water? Cutoffs? PME? -- --- Erik Marklund, PhD student Dept. of Cell and Molecular Biology, Uppsala University. Husargatan 3, Box 596,75124 Uppsala, Sweden phone:+46 18 471 4537fax: +46 18 511 755 er...@xray.bmc.uu.sehttp://folding.bmc.uu.se/ -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php
Re: [gmx-users] enegry minimisation
Thanks Justin for your reply. Yes I have included solvent in the protein using genbox. I am pasting .mdp file which I used for MD simulation : title = trp_drg MD cpp = /lib/cpp ; location of cpp on SGI constraints = all-bonds integrator = md dt = 0.002 ; ps ! nsteps = 50 ; total 1 ns. nstcomm =1 nstxout = 500 ; output coordinates every 1.0 ps nstvout =0 nstfout =0 nstlist = 5 ns_type = grid rlist = 0.9 coulombtype = PME rcoulomb = 0.9 rvdw = 1.4 fourierspacing = 0.12 fourier_nx =0 fourier_ny =0 fourier_nz =0 pme_order =6 ewald_rtol = 1e-5 optimize_fft = yes ; Berendsen temperature coupling is on in four groups Tcoupl = berendsen tau_t = 0.1 0.1 0.1 0.1 0.1 0.1 tc_grps = Protein SOL MG PEP E4P NA+ ref_t = 300 300 300 300 300 300 ; Pressure coupling is on Pcoupl = berendsen pcoupltype = isotropic tau_p = 0.5 compressibility = 4.5e-5 ref_p = 1.0 ; Generate velocites is on at 300 K. gen_vel = yes gen_temp = 300.0 gen_seed = 173529 I hope it will help you to guide me futher. Thanks -- Sonali Dhindwal --- On Wed, 19/5/10, Justin A. Lemkul jalem...@vt.edu wrote: From: Justin A. Lemkul jalem...@vt.edu Subject: Re: [gmx-users] enegry minimisation To: Discussion list for GROMACS users gmx-users@gromacs.org Date: Wednesday, 19 May, 2010, 5:17 PM sonali dhindwal wrote: Hello All This question may sound trivial to many, but as i am new to this field, please help. I want to ask a question regarding my previous query of distortion of protein strucutre after molecular dynamcs simulation. Can you provide a link to your previous post, for reference? I have noticed that after enegry minimisation using steepest decent algorithm, using emtol of 1000 kJ mol^-1 nm^-1 . So is it necessary to do enegry minimisation step before MD, because this is my modeled protein, and i have already done energy minimisation using different program and after that I have done refinement also. Have you added solvent or anything else to the protein model? If so, then the answer is yes. Solvation with a regularly-ordered lattice of solvent molecules can (and often does) lead to bad clashes with your protein structure, thus necessitating further minimization. There are plenty of reasons why a protein structure might be unstable, most of them related to .mdp file settings, but you haven't posted those so there's no way to know if you're doing things correctly. -Justin Thanks and regards ^ -- Sonali Dhindwal -- Justin A. Lemkul Ph.D. Candidate ICTAS Doctoral Scholar MILES-IGERT Trainee Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu | (540) 231-9080 http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin -- gmx-users mailing list gmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php
Re: [gmx-users] enegry minimisation
sonali dhindwal wrote: Thanks Justin for your reply. Yes I have included solvent in the protein using genbox. Then you should do energy minimization after constructing the system. I am pasting .mdp file which I used for MD simulation : title = trp_drg MD cpp = /lib/cpp ; location of cpp on SGI constraints = all-bonds integrator = md dt = 0.002 ; ps ! nsteps = 50 ; total 1 ns. nstcomm =1 I don't know if this matters or not, but I think your parameters and values should be separated from the '=' by whitespace. I also don't know if that will have any effect on your unstable system (see below), but do check to make sure that all of your settings have been interpreted correctly. Confirm your input settings with the mdout.mdp file produced by grompp. nstxout = 500 ; output coordinates every 1.0 ps nstvout =0 nstfout =0 nstlist = 5 ns_type = grid rlist = 0.9 coulombtype = PME rcoulomb= 0.9 rvdw= 1.4 fourierspacing = 0.12 fourier_nx=0 fourier_ny=0 fourier_nz=0 pme_order =6 ewald_rtol= 1e-5 optimize_fft = yes ; Berendsen temperature coupling is on in four groups Tcoupl= berendsen tau_t = 0.10.1 0.1 0.1 0.1 0.1 tc_grps = ProteinSOLMG PEP E4P NA+ ref_t = 300300 300 300 300 300 This thermostat setup is certainly incorrect. You should not couple all the components of your system to separate thermostats. See here: http://www.gromacs.org/Documentation/Terminology/Thermostats You have a fairly complicated system. Are some of these species small molecules? If so, how did you derive their parameters? Have you demonstrated that these parameters are accurate? Which structure is falling apart, and how are you making that assessment? -Justin ; Pressure coupling is on Pcoupl = berendsen pcoupltype = isotropic tau_p = 0.5 compressibility = 4.5e-5 ref_p = 1.0 ; Generate velocites is on at 300 K. gen_vel = yes gen_temp = 300.0 gen_seed = 173529 I hope it will help you to guide me futher. Thanks -- Sonali Dhindwal --- On *Wed, 19/5/10, Justin A. Lemkul /jalem...@vt.edu/* wrote: From: Justin A. Lemkul jalem...@vt.edu Subject: Re: [gmx-users] enegry minimisation To: Discussion list for GROMACS users gmx-users@gromacs.org Date: Wednesday, 19 May, 2010, 5:17 PM sonali dhindwal wrote: Hello All This question may sound trivial to many, but as i am new to this field, please help. I want to ask a question regarding my previous query of distortion of protein strucutre after molecular dynamcs simulation. Can you provide a link to your previous post, for reference? I have noticed that after enegry minimisation using steepest decent algorithm, using emtol of 1000 kJ mol^-1 nm^-1 . So is it necessary to do enegry minimisation step before MD, because this is my modeled protein, and i have already done energy minimisation using different program and after that I have done refinement also. Have you added solvent or anything else to the protein model? If so, then the answer is yes. Solvation with a regularly-ordered lattice of solvent molecules can (and often does) lead to bad clashes with your protein structure, thus necessitating further minimization. There are plenty of reasons why a protein structure might be unstable, most of them related to .mdp file settings, but you haven't posted those so there's no way to know if you're doing things correctly. -Justin Thanks and regards ^ -- Sonali Dhindwal -- Justin A. Lemkul Ph.D. Candidate ICTAS Doctoral Scholar MILES-IGERT Trainee Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu | (540) 231-9080 http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin -- gmx-users mailing listgmx-users@gromacs.org /mc/compose?to=gmx-us...@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org /mc/compose?to=gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php -- Justin A. Lemkul Ph.D. Candidate ICTAS Doctoral Scholar MILES-IGERT Trainee Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu
Re: [gmx-users] enegry minimisation
Sorry, but I couldnt get your question, I have used this .mdp file for energy minimisation after addition of water and using GROMOS96 43a1 force field : title = drg_trp cpp = /lib/cpp ; location of cpp on SGI define = -DFLEX_SPC ; Use Ferguson’s Flexible water model [4] constraints = none integrator = steep dt = 0.002 ; ps ! nsteps = 2000 nstlist = 10 ns_type = grid rlist = 0.9 coulombtype = PME ; Use particle-mesh ewald rcoulomb = 0.9 rvdw = 1.0 fourierspacing = 0.12 fourier_nx = 0 fourier_ny = 0 fourier_nz = 0 pme_order = 4 ewald_rtol = 1e-5 optimize_fft = yes ; ; Energy minimizing stuff ; emtol = 1000.0 emstep = 0.01 I hope it will help you to guide me further Thanks -- Sonali Dhindwal --- On Wed, 19/5/10, Erik Marklund er...@xray.bmc.uu.se wrote: From: Erik Marklund er...@xray.bmc.uu.se Subject: Re: [gmx-users] enegry minimisation To: Discussion list for GROMACS users gmx-users@gromacs.org Date: Wednesday, 19 May, 2010, 5:31 PM sonali dhindwal skrev: Hello All This question may sound trivial to many, but as i am new to this field, please help. I want to ask a question regarding my previous query of distortion of protein strucutre after molecular dynamcs simulation. I have noticed that after enegry minimisation using steepest decent algorithm, using emtol of 1000 kJ mol^-1 nm^-1 , large amount of distortion occurs. So is it necessary to do enegry minimisation step before MD, because this is my modeled protein, and i have already done energy minimisation using different program and after that I have done refinement also. Thanks and regards ^ -- Sonali Dhindwal So how has your system setup changed since your previous EM? Addition of water? Cutoffs? PME? -- --- Erik Marklund, PhD student Dept. of Cell and Molecular Biology, Uppsala University. Husargatan 3, Box 596, 75124 Uppsala, Sweden phone: +46 18 471 4537 fax: +46 18 511 755 er...@xray.bmc.uu.se http://folding.bmc.uu.se/ -- gmx-users mailing list gmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php
Re: [gmx-users] enegry minimisation
After adding water you can do energy minimization (EM) in two steps: 1. Constrain the protein backbone and do EM. 2. Now do EM on the full system. 3. Run a short MD simulation by constraining the protein backbone. The above three steps will help hydrate the protein molecule with minimal distortion of protein structure. 4. Now run a MD on full system. for details looks here: http://www.google.com/url?sa=tsource=webct=rescd=2ved=0CBcQFjABurl=http%3A%2F%2Feugen.leitl.org%2Fchem%2Fkerrigje%2Fpdf_files%2Ffwspidr_tutor.pdfei=jOPzS8a3Lab2MdX1_aAOusg=AFQjCNGB_3mXSQRHuqehBSHXsRyXP1Gymgsig2=bY3NqXHmruR7eSLVyAuCHQ -Gaurav On Wed, May 19, 2010 at 8:18 AM, sonali dhindwal sonali11dhind...@yahoo.co.in wrote: Sorry, but I couldnt get your question, I have used this .mdp file for energy minimisation after addition of water and using GROMOS96 43a1 force field : title= drg_trp cpp = /lib/cpp ; location of cpp on SGI define = -DFLEX_SPC ; Use Ferguson’s Flexible water model [4] constraints = none integrator = steep dt = 0.002; ps ! nsteps = 2000 nstlist = 10 ns_type = grid rlist= 0.9 coulombtype = PME ; Use particle-mesh ewald rcoulomb = 0.9 rvdw = 1.0 fourierspacing = 0.12 fourier_nx = 0 fourier_ny = 0 fourier_nz = 0 pme_order = 4 ewald_rtol = 1e-5 optimize_fft = yes ; ; Energy minimizing stuff ; emtol = 1000.0 emstep = 0.01 I hope it will help you to guide me further Thanks -- Sonali Dhindwal --- On *Wed, 19/5/10, Erik Marklund er...@xray.bmc.uu.se* wrote: From: Erik Marklund er...@xray.bmc.uu.se Subject: Re: [gmx-users] enegry minimisation To: Discussion list for GROMACS users gmx-users@gromacs.org Date: Wednesday, 19 May, 2010, 5:31 PM sonali dhindwal skrev: Hello All This question may sound trivial to many, but as i am new to this field, please help. I want to ask a question regarding my previous query of distortion of protein strucutre after molecular dynamcs simulation. I have noticed that after enegry minimisation using steepest decent algorithm, using emtol of 1000 kJ mol^-1 nm^-1 , large amount of distortion occurs. So is it necessary to do enegry minimisation step before MD, because this is my modeled protein, and i have already done energy minimisation using different program and after that I have done refinement also. Thanks and regards ^ -- Sonali Dhindwal So how has your system setup changed since your previous EM? Addition of water? Cutoffs? PME? -- --- Erik Marklund, PhD student Dept. of Cell and Molecular Biology, Uppsala University. Husargatan 3, Box 596,75124 Uppsala, Sweden phone:+46 18 471 4537fax: +46 18 511 755 er...@xray.bmc.uu.se http://mc/compose?to=er...@xray.bmc.uu.se http://folding.bmc.uu.se/ -- gmx-users mailing list gmx-users@gromacs.orghttp://mc/compose?to=gmx-us...@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.orghttp://mc/compose?to=gmx-users-requ...@gromacs.org . Can't post? Read http://www.gromacs.org/mailing_lists/users.php -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php
Re: [gmx-users] enegry minimisation
Gaurav Goel wrote: After adding water you can do energy minimization (EM) in two steps: 1. Constrain the protein backbone and do EM. 2. Now do EM on the full system. 3. Run a short MD simulation by constraining the protein backbone. The above three steps will help hydrate the protein molecule with minimal distortion of protein structure. Such finesse may certainly be beneficial. Just for clarity, though, what you are referring to is the application of (position) restraints, not constraints. http://www.gromacs.org/Documentation/Terminology/Constraints_and_Restraints -Justin 4. Now run a MD on full system. for details looks here: http://www.google.com/url?sa=tsource=webct=rescd=2ved=0CBcQFjABurl=http%3A%2F%2Feugen.leitl.org%2Fchem%2Fkerrigje%2Fpdf_files%2Ffwspidr_tutor.pdfei=jOPzS8a3Lab2MdX1_aAOusg=AFQjCNGB_3mXSQRHuqehBSHXsRyXP1Gymgsig2=bY3NqXHmruR7eSLVyAuCHQ http://www.google.com/url?sa=tsource=webct=rescd=2ved=0CBcQFjABurl=http%3A%2F%2Feugen.leitl.org%2Fchem%2Fkerrigje%2Fpdf_files%2Ffwspidr_tutor.pdfei=jOPzS8a3Lab2MdX1_aAOusg=AFQjCNGB_3mXSQRHuqehBSHXsRyXP1Gymgsig2=bY3NqXHmruR7eSLVyAuCHQ -Gaurav On Wed, May 19, 2010 at 8:18 AM, sonali dhindwal sonali11dhind...@yahoo.co.in mailto:sonali11dhind...@yahoo.co.in wrote: Sorry, but I couldnt get your question, I have used this .mdp file for energy minimisation after addition of water and using GROMOS96 43a1 force field : title= drg_trp cpp = /lib/cpp ; location of cpp on SGI define = -DFLEX_SPC ; Use Ferguson’s Flexible water model [4] constraints = none integrator = steep dt = 0.002; ps ! nsteps = 2000 nstlist = 10 ns_type = grid rlist= 0.9 coulombtype = PME ; Use particle-mesh ewald rcoulomb = 0.9 rvdw = 1.0 fourierspacing = 0.12 fourier_nx = 0 fourier_ny = 0 fourier_nz = 0 pme_order = 4 ewald_rtol = 1e-5 optimize_fft = yes ; ; Energy minimizing stuff ; emtol = 1000.0 emstep = 0.01 I hope it will help you to guide me further Thanks -- Sonali Dhindwal --- On *Wed, 19/5/10, Erik Marklund /er...@xray.bmc.uu.se mailto:er...@xray.bmc.uu.se/* wrote: From: Erik Marklund er...@xray.bmc.uu.se mailto:er...@xray.bmc.uu.se Subject: Re: [gmx-users] enegry minimisation To: Discussion list for GROMACS users gmx-users@gromacs.org mailto:gmx-users@gromacs.org Date: Wednesday, 19 May, 2010, 5:31 PM sonali dhindwal skrev: Hello All This question may sound trivial to many, but as i am new to this field, please help. I want to ask a question regarding my previous query of distortion of protein strucutre after molecular dynamcs simulation. I have noticed that after enegry minimisation using steepest decent algorithm, using emtol of 1000 kJ mol^-1 nm^-1 , large amount of distortion occurs. So is it necessary to do enegry minimisation step before MD, because this is my modeled protein, and i have already done energy minimisation using different program and after that I have done refinement also. Thanks and regards ^ -- Sonali Dhindwal So how has your system setup changed since your previous EM? Addition of water? Cutoffs? PME? -- --- Erik Marklund, PhD student Dept. of Cell and Molecular Biology, Uppsala University. Husargatan 3, Box 596,75124 Uppsala, Sweden phone:+46 18 471 4537fax: +46 18 511 755 er...@xray.bmc.uu.se http://mc/compose?to=er...@xray.bmc.uu.se http://folding.bmc.uu.se/ -- gmx-users mailing listgmx-users@gromacs.org http://mc/compose?to=gmx-us...@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org http://mc/compose?to=gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php -- gmx-users mailing listgmx-users@gromacs.org mailto:gmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org mailto:gmx-users-requ...@gromacs.org. Can't post? Read http
Re: [gmx-users] enegry minimisation
On Wed, May 19, 2010 at 9:18 AM, Justin A. Lemkul jalem...@vt.edu wrote: Gaurav Goel wrote: After adding water you can do energy minimization (EM) in two steps: 1. Constrain the protein backbone and do EM. 2. Now do EM on the full system. 3. Run a short MD simulation by constraining the protein backbone. The above three steps will help hydrate the protein molecule with minimal distortion of protein structure. Such finesse may certainly be beneficial. Just for clarity, though, what you are referring to is the application of (position) restraints, not constraints. http://www.gromacs.org/Documentation/Terminology/Constraints_and_Restraints Justin, thanks for clarifying. I was referring to position restraints. -Gaurav -Justin 4. Now run a MD on full system. for details looks here: http://www.google.com/url?sa=tsource=webct=rescd=2ved=0CBcQFjABurl=http%3A%2F%2Feugen.leitl.org%2Fchem%2Fkerrigje%2Fpdf_files%2Ffwspidr_tutor.pdfei=jOPzS8a3Lab2MdX1_aAOusg=AFQjCNGB_3mXSQRHuqehBSHXsRyXP1Gymgsig2=bY3NqXHmruR7eSLVyAuCHQ http://www.google.com/url?sa=tsource=webct=rescd=2ved=0CBcQFjABurl=http%3A%2F%2Feugen.leitl.org%2Fchem%2Fkerrigje%2Fpdf_files%2Ffwspidr_tutor.pdfei=jOPzS8a3Lab2MdX1_aAOusg=AFQjCNGB_3mXSQRHuqehBSHXsRyXP1Gymgsig2=bY3NqXHmruR7eSLVyAuCHQ -Gaurav On Wed, May 19, 2010 at 8:18 AM, sonali dhindwal sonali11dhind...@yahoo.co.in mailto:sonali11dhind...@yahoo.co.in wrote: Sorry, but I couldnt get your question, I have used this .mdp file for energy minimisation after addition of water and using GROMOS96 43a1 force field : title = drg_trp cpp = /lib/cpp ; location of cpp on SGI define = -DFLEX_SPC ; Use Ferguson’s Flexible water model [4] constraints = none integrator = steep dt = 0.002 ; ps ! nsteps = 2000 nstlist = 10 ns_type = grid rlist = 0.9 coulombtype = PME ; Use particle-mesh ewald rcoulomb = 0.9 rvdw = 1.0 fourierspacing = 0.12 fourier_nx = 0 fourier_ny = 0 fourier_nz = 0 pme_order = 4 ewald_rtol = 1e-5 optimize_fft = yes ; ; Energy minimizing stuff ; emtol = 1000.0 emstep = 0.01 I hope it will help you to guide me further Thanks -- Sonali Dhindwal --- On *Wed, 19/5/10, Erik Marklund /er...@xray.bmc.uu.se mailto:er...@xray.bmc.uu.se/* wrote: From: Erik Marklund er...@xray.bmc.uu.se mailto:er...@xray.bmc.uu.se Subject: Re: [gmx-users] enegry minimisation To: Discussion list for GROMACS users gmx-users@gromacs.org mailto:gmx-users@gromacs.org Date: Wednesday, 19 May, 2010, 5:31 PM sonali dhindwal skrev: Hello All This question may sound trivial to many, but as i am new to this field, please help. I want to ask a question regarding my previous query of distortion of protein strucutre after molecular dynamcs simulation. I have noticed that after enegry minimisation using steepest decent algorithm, using emtol of 1000 kJ mol^-1 nm^-1 , large amount of distortion occurs. So is it necessary to do enegry minimisation step before MD, because this is my modeled protein, and i have already done energy minimisation using different program and after that I have done refinement also. Thanks and regards ^ -- Sonali Dhindwal So how has your system setup changed since your previous EM? Addition of water? Cutoffs? PME? -- --- Erik Marklund, PhD student Dept. of Cell and Molecular Biology, Uppsala University. Husargatan 3, Box 596, 75124 Uppsala, Sweden phone: +46 18 471 4537 fax: +46 18 511 755 er...@xray.bmc.uu.se http://mc/compose?to=er...@xray.bmc.uu.se http://folding.bmc.uu.se/ -- gmx-users mailing list gmx-us...@gromacs.org http://mc/compose?to=gmx-us...@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org http://mc/compose?to=gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php -- gmx-users mailing list gmx-us...@gromacs.org mailto:gmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list
Re: [gmx-users] enegry minimisation
Thanks Justin for your help I checked the mdout.mpd, all the parameters were interpereted correctly, though from next time i will take care of putting space. regarding you asked if those are small molecules, yes those are the ligands and i have taken .itp and .gro file from Dundee Prodrg server. I think those are acceptable !! Thermostat setup: I will now do this thing seperately as protein and non protein only as given in manual. And also I will do that thing suggested by Gaurav, hopefully it will help in not distorting the protein structure. Thanks a lot. -- Sonali Dhindwal --- On Wed, 19/5/10, Justin A. Lemkul jalem...@vt.edu wrote: From: Justin A. Lemkul jalem...@vt.edu Subject: Re: [gmx-users] enegry minimisation To: Gromacs Users' List gmx-users@gromacs.org Date: Wednesday, 19 May, 2010, 5:45 PM sonali dhindwal wrote: Thanks Justin for your reply. Yes I have included solvent in the protein using genbox. Then you should do energy minimization after constructing the system. I am pasting .mdp file which I used for MD simulation : title = trp_drg MD cpp = /lib/cpp ; location of cpp on SGI constraints = all-bonds integrator = md dt = 0.002 ; ps ! nsteps = 50 ; total 1 ns. nstcomm =1 I don't know if this matters or not, but I think your parameters and values should be separated from the '=' by whitespace. I also don't know if that will have any effect on your unstable system (see below), but do check to make sure that all of your settings have been interpreted correctly. Confirm your input settings with the mdout.mdp file produced by grompp. nstxout = 500 ; output coordinates every 1.0 ps nstvout =0 nstfout =0 nstlist = 5 ns_type = grid rlist = 0.9 coulombtype = PME rcoulomb = 0.9 rvdw = 1.4 fourierspacing = 0.12 fourier_nx =0 fourier_ny =0 fourier_nz =0 pme_order =6 ewald_rtol = 1e-5 optimize_fft = yes ; Berendsen temperature coupling is on in four groups Tcoupl = berendsen tau_t = 0.1 0.1 0.1 0.1 0.1 0.1 tc_grps = Protein SOL MG PEP E4P NA+ ref_t = 300 300 300 300 300 300 This thermostat setup is certainly incorrect. You should not couple all the components of your system to separate thermostats. See here: http://www.gromacs.org/Documentation/Terminology/Thermostats You have a fairly complicated system. Are some of these species small molecules? If so, how did you derive their parameters? Have you demonstrated that these parameters are accurate? Which structure is falling apart, and how are you making that assessment? -Justin ; Pressure coupling is on Pcoupl = berendsen pcoupltype = isotropic tau_p = 0.5 compressibility = 4.5e-5 ref_p = 1.0 ; Generate velocites is on at 300 K. gen_vel = yes gen_temp = 300.0 gen_seed = 173529 I hope it will help you to guide me futher. Thanks -- Sonali Dhindwal --- On *Wed, 19/5/10, Justin A. Lemkul /jalem...@vt.edu/* wrote: From: Justin A. Lemkul jalem...@vt.edu Subject: Re: [gmx-users] enegry minimisation To: Discussion list for GROMACS users gmx-users@gromacs.org Date: Wednesday, 19 May, 2010, 5:17 PM sonali dhindwal wrote: Hello All This question may sound trivial to many, but as i am new to this field, please help. I want to ask a question regarding my previous query of distortion of protein strucutre after molecular dynamcs simulation. Can you provide a link to your previous post, for reference? I have noticed that after enegry minimisation using steepest decent algorithm, using emtol of 1000 kJ mol^-1 nm^-1 . So is it necessary to do enegry minimisation step before MD, because this is my modeled protein, and i have already done energy minimisation using different program and after that I have done refinement also. Have you added solvent or anything else to the protein model? If so, then the answer is yes. Solvation with a regularly-ordered lattice of solvent molecules can (and often does) lead to bad clashes with your protein structure, thus necessitating further minimization. There are plenty of reasons why a protein structure might be unstable, most of them related to .mdp file settings, but you haven't posted those so there's no way to know if you're doing things correctly. -Justin Thanks and regards ^ -- Sonali Dhindwal -- Justin A. Lemkul Ph.D. Candidate ICTAS Doctoral Scholar
Re: [gmx-users] enegry minimisation
sonali dhindwal wrote: Thanks Justin for your help I checked the mdout.mpd, all the parameters were interpereted correctly, though from next time i will take care of putting space. regarding you asked if those are small molecules, yes those are the ligands and i have taken .itp and .gro file from Dundee Prodrg server. I think those are acceptable !! I seem to say this several times per week: in my experience (and in the experience of many others who have posted here) the charges and charge groups output by PRODRG are often unsatisfactory, requiring manual modification and validation that they are correct. This should be absolutely requisite for any study involving non-standard small molecules. Increasingly, I see poor parameters used in the literature and it always makes me wonder how the simulations can be regarded as valid. There should be no shortcuts - parameterization of small molecules is an advanced topic, requiring great care and understanding of the underlying force field. http://www.gromacs.org/Documentation/How-tos/Parameterization I don't mean to undermine PRODRG entirely - it is a very useful tool for generating a framework topology. But I have yet to see a topology it produced that is at all consistent with the parameters in the Gromos96 force field. Try it yourself - run a known species (like an amino acid) through PRODRG. The results it gives are usually wildly inconsistent with the force field parameter library. -Justin Thermostat setup: I will now do this thing seperately as protein and non protein only as given in manual. And also I will do that thing suggested by Gaurav, hopefully it will help in not distorting the protein structure. Thanks a lot. -- Sonali Dhindwal --- On *Wed, 19/5/10, Justin A. Lemkul /jalem...@vt.edu/* wrote: From: Justin A. Lemkul jalem...@vt.edu Subject: Re: [gmx-users] enegry minimisation To: Gromacs Users' List gmx-users@gromacs.org Date: Wednesday, 19 May, 2010, 5:45 PM sonali dhindwal wrote: Thanks Justin for your reply. Yes I have included solvent in the protein using genbox. Then you should do energy minimization after constructing the system. I am pasting .mdp file which I used for MD simulation : title = trp_drg MD cpp = /lib/cpp ; location of cpp on SGI constraints = all-bonds integrator = md dt = 0.002 ; ps ! nsteps = 50 ; total 1 ns. nstcomm =1 I don't know if this matters or not, but I think your parameters and values should be separated from the '=' by whitespace. I also don't know if that will have any effect on your unstable system (see below), but do check to make sure that all of your settings have been interpreted correctly. Confirm your input settings with the mdout.mdp file produced by grompp. nstxout = 500 ; output coordinates every 1.0 ps nstvout =0 nstfout =0 nstlist = 5 ns_type = grid rlist = 0.9 coulombtype = PME rcoulomb= 0.9 rvdw= 1.4 fourierspacing = 0.12 fourier_nx=0 fourier_ny=0 fourier_nz=0 pme_order =6 ewald_rtol= 1e-5 optimize_fft = yes ; Berendsen temperature coupling is on in four groups Tcoupl= berendsen tau_t = 0.10.1 0.1 0.1 0.1 0.1 tc_grps = ProteinSOLMG PEP E4P NA+ ref_t = 300300 300 300 300 300 This thermostat setup is certainly incorrect. You should not couple all the components of your system to separate thermostats. See here: http://www.gromacs.org/Documentation/Terminology/Thermostats You have a fairly complicated system. Are some of these species small molecules? If so, how did you derive their parameters? Have you demonstrated that these parameters are accurate? Which structure is falling apart, and how are you making that assessment? -Justin ; Pressure coupling is on Pcoupl = berendsen pcoupltype = isotropic tau_p = 0.5 compressibility = 4.5e-5 ref_p = 1.0 ; Generate velocites is on at 300 K. gen_vel = yes gen_temp = 300.0 gen_seed = 173529 I hope it will help you to guide me futher. Thanks -- Sonali Dhindwal --- On *Wed, 19/5/10, Justin A. Lemkul /jalem...@vt.edu/* wrote: From: Justin A. Lemkul jalem...@vt.edu Subject: Re: [gmx-users] enegry minimisation To: Discussion list for GROMACS users gmx-users@gromacs.org
RE: [gmx-users] enegry minimisation
I seem to say this several times per week: in my experience (and in the experience of many others who have posted here) the charges and charge groups output by PRODRG are often unsatisfactory, requiring manual Might be an idea then to put the comments on the PRODRG page on the GROMACS website / wiki and direct people there? Catch ya, Dr. Dallas Warren Drug Delivery, Disposition and Dynamics Monash Institute of Pharmaceutical Sciences, Monash University 381 Royal Parade, Parkville VIC 3010 dallas.war...@pharm.monash.edu.au +61 3 9903 9167 - When the only tool you own is a hammer, every problem begins to resemble a nail. -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php
Re: [gmx-users] enegry minimisation
Dallas B. Warren wrote: I seem to say this several times per week: in my experience (and in the experience of many others who have posted here) the charges and charge groups output by PRODRG are often unsatisfactory, requiring manual Might be an idea then to put the comments on the PRODRG page on the GROMACS website / wiki and direct people there? Excellent idea. Done and done. http://www.gromacs.org/index.php?title=Download_%26_Installation/Related_Software/PRODRG#Tips -Justin Catch ya, Dr. Dallas Warren Drug Delivery, Disposition and Dynamics Monash Institute of Pharmaceutical Sciences, Monash University 381 Royal Parade, Parkville VIC 3010 dallas.war...@pharm.monash.edu.au +61 3 9903 9167 - When the only tool you own is a hammer, every problem begins to resemble a nail. -- Justin A. Lemkul Ph.D. Candidate ICTAS Doctoral Scholar MILES-IGERT Trainee Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu | (540) 231-9080 http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin -- gmx-users mailing listgmx-users@gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org. Can't post? Read http://www.gromacs.org/mailing_lists/users.php
